Capillary electrophoresis is a powerful analytical separation technique that brings speed, quantitation, reproducibility and automation to the inherently highly resolving but typically labor intensive methods of electrophoresis (e.g., Capillary Electrophoresis Theory and Practice, Grossman and Colburn, eds., Academic Press (1992)). While early capillary electrophoresis systems utilized only a single capillary tube, multi-channel systems have been developed to provide increased throughput (e.g., Mathies et al., U.S. Pat. No. 5,247,240; Dovichi and Zhang, U.S. Pat. No. 5,439,578; Kambara, U.S. Pat. No. 5,516,406; Takahashi, et al., Anal. Chem., 66:1021-1026 (1994)). Such multi-channel systems are particularly attractive for use in large scale DNA sequencing projects.
In conventional multi-capillary capillary electrophoresis systems, samples are introduced in the capillaries by dipping the capillary inlets into samples contained in a plurality of sample reservoirs. However, this method of sample introduction has several disadvantages, particularly for applications requiring a high degree of automation, throughput and reliability. First, these existing systems require a one-to-one correspondence between a given sample well location and a given capillary tube. That is, samples located in a given sample well will always be analyzed by a given corresponding capillary tube. This is problematic because if a capillary tube becomes non-operational, samples located in wells corresponding to that capillary tube will not be analyzed until that capillary is replaced. Second, in order for the capillary inlets to be dipped into the sample wells, the pitch, or spacing, of the capillary inlets must match the pitch of the sample wells. This constrains the sample well formats that may be used, and requires the capillary spacing to be dictated by the sample well configuration rather than the requirements of the analyzer. Also, because existing sample handling systems rely on the capillary tubes to be dipped into a sample well, these systems require discrete capillaries to be used rather than capillaries formed in a monolithic substrate. Finally, existing sample handling systems require a relative motion between the capillary tubes and the sample well after the sample has been injected into the capillary tubes, i.e., the capillary is removed from the sample wells, or the sample wells are removed from the capillary tubes. This relative motion may disrupt the injected sample as a result of agitation and/or evaporation such that electrophoretic resolution of the sample components is compromised.
Thus, it would be desirable to provide a sample handling system for a multi-channel capillary electrophoresis device that addresses the above disadvantages of traditional devices.